{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:37:43Z","timestamp":1790764663150,"version":"4.1.0"},"reference-count":25,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Initiative Alle-Lieben-Schmidt e.V.","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"Initiative Alle-Lieben-Schmidt e.V.","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative e.V","doi-asserted-by":"publisher","award":["21060"],"award-info":[{"award-number":["21060"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative e.V","doi-asserted-by":"publisher","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hertie Network of Excellence in Clinical Neuroscience","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"Hertie Network of Excellence in Clinical Neuroscience","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]},{"name":"BONFOR-Forschungskommission der Medizinischen Fakult\u00e4t Bonn and by the Deutsche Forschungsgemeinschaft","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"BONFOR-Forschungskommission der Medizinischen Fakult\u00e4t Bonn and by the Deutsche Forschungsgemeinschaft","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]},{"name":"Neuro-aCSis Bonn Neuroscience Clinician Scientist Program","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"Neuro-aCSis Bonn Neuroscience Clinician Scientist Program","award":["2021-1A-12"],"award-info":[{"award-number":["2021-1A-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is an invariably fatal neurodegenerative disease with limited therapeutic options. There is an urgent need for novel biomarkers to be used as surrogates for new therapeutic trials and disease monitoring. In this study, we sought to systematically study creatine kinase isoenzyme MB (CK-MB) in a real-world cohort of ALS patients, assess the diagnostic performance, and evaluate its association with other laboratory and clinical parameters. We reviewed data from 194 consecutive patients that included 130 ALS patients and 64 disease control patients (primary lateral sclerosis [PLS], benign fasciculations syndrome [BFS], Huntington\u2019s disease [HD] and Alzheimer\u2019s disease [AD]). CK-MB was elevated in the sera of more than half of all patients with ALS. In patients with spinal-onset ALS, CK-MB levels were significantly higher than in patients with other neurodegenerative diseases. Patients with slower rates of functional decline had a significantly higher baseline CK-MB. Furthermore, CK-MB elevations correlated with cardiac troponin T (cTnT) and with revised ALS Functional Rating Scale (ALSFRS-R) bulbar subcategory. We posit that measuring CK-MB in ALS patients in a complimentary fashion could potentially aid in the diagnostic workup of ALS and help discriminate the disease from some ALS mimics and other neurodegenerative diseases. CK-MB levels also may provide valuable prognostic information regarding disease aggressiveness as well as correlations with specific phenotypic presentations.<\/jats:p>","DOI":"10.3390\/ijms241411682","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T04:27:13Z","timestamp":1689827233000},"page":"11682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Creatine Kinase MB Isoenzyme Is a Complementary Biomarker in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Natsinee","family":"Kittipeerapat","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Diseases\/Neurology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Fabian","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases\/Neurology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bernsen","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases\/Neurology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2344-5662","authenticated-orcid":false,"given":"Patrick","family":"Weydt","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases\/Neurology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1581-474X","authenticated-orcid":false,"given":"Sergio","family":"Castro-Gomez","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases\/Neurology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"},{"name":"Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S1474-4422(21)00465-8","article-title":"Recent Advances in the Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/21678421.2022.2150555","article-title":"The Future of ALS Diagnosis and Staging: Where Do We Go from Here?","volume":"24","author":"Genge","year":"2023","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and Creatinine Metabolism","volume":"80","author":"Wyss","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5395","DOI":"10.1007\/s00415-022-11195-8","article-title":"Creatine Kinase and Prognosis in Amyotrophic Lateral Sclerosis: A Literature Review and Multi-Centre Cohort Analysis","volume":"269","author":"Gao","year":"2022","journal-title":"J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0006-291X(65)90200-7","article-title":"Creatine Kinase: Evidence for a Dimeric Structure","volume":"21","author":"Dawson","year":"1965","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1161\/CIRCULATIONAHA.108.773218","article-title":"Requiem for a Heavyweight: The Demise of Creatine Kinase-MB","volume":"118","author":"Saenger","year":"2008","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0009-9120(79)80108-3","article-title":"Creatine-Kinase and CK-MB Isoenzyme Activity in Serum of Patients after Surgical Operations, Polytrauma and Other Damage to Skeletal Muscle","volume":"12","author":"Prellwitz","year":"1979","journal-title":"Clin. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1001\/jamainternmed.2017.3597","article-title":"Eliminating Creatine Kinase\u2013Myocardial Band Testing in Suspected Acute Coronary Syndrome: A Value-Based Quality Improvement","volume":"177","author":"Alvin","year":"2017","journal-title":"JAMA Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"fcab274","DOI":"10.1093\/braincomms\/fcab274","article-title":"Teaching an Old Dog New Tricks: Serum Troponin T as a Biomarker in Amyotrophic Lateral Sclerosis","volume":"3","author":"Radermacher","year":"2021","journal-title":"Brain Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0009-8981(76)90322-3","article-title":"Serum Creatine Kinase Isoenzyme Pattern in Nervous System Atrophies and Neuromuscular Disorders","volume":"73","author":"Grabert","year":"1976","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/BF00313786","article-title":"Serum Creatine Kinase B Subunit Levels in Neurogenic Atrophies","volume":"232","author":"Vassilopoulos","year":"1985","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3109\/21678421.2015.1062516","article-title":"Relationship of Creatine Kinase to Body Composition, Disease State, and Longevity in ALS","volume":"16","author":"Gibson","year":"2015","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3389\/fneur.2017.00322","article-title":"Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis","volume":"8","author":"Tai","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102094","DOI":"10.1016\/j.nicl.2019.102094","article-title":"Applying the D50 Disease Progression Model to Gray and White Matter Pathology in Amyotrophic Lateral Sclerosis","volume":"25","author":"Steinbach","year":"2020","journal-title":"Neuroimage Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/21678421.2021.1939384","article-title":"Cardiac Troponin T Is Elevated and Increases Longitudinally in ALS Patients","volume":"23","author":"Chamoun","year":"2022","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.jacc.2014.03.027","article-title":"Elevation of Cardiac Troponin T, but Not Cardiac Troponin I, in Patients with Neuromuscular Diseases: Implications for the Diagnosis of Myocardial Infarction","volume":"63","author":"Rittoo","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s13760-017-0855-y","article-title":"Serum Troponin T in Patients with Amyotrophic Lateral Sclerosis","volume":"119","author":"Casmiro","year":"2019","journal-title":"Acta Neurol. Belg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3389\/fneur.2017.00479","article-title":"Cardiac Findings in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Imaging Study","volume":"8","author":"Rosenbohm","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1159\/000458585","article-title":"Serum Creatine Kinase Isoenzymes in Progressive MuscularDystrophy","volume":"23","author":"Tzvetanova","year":"1978","journal-title":"Enzyme"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.4081\/bam.2014.1.5","article-title":"The Biology of Long-Term Denervated Skeletal Muscle","volume":"24","author":"Carlson","year":"2014","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.nmd.2006.06.006","article-title":"Raised Troponin T in Inclusion Body Myositis Is Common and Serum Levels Are Persistent over Time","volume":"16","author":"Lindberg","year":"2006","journal-title":"Neuromuscul. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/00000441-198205000-00011","article-title":"Case Report CK-MB Isoenzyme in Patients with Polymyositis","volume":"283","author":"Tsung","year":"1982","journal-title":"Am. J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.clinph.2007.09.143","article-title":"Electrodiagnostic Criteria for Diagnosis of ALS","volume":"119","author":"Dengler","year":"2008","journal-title":"Clin. Neurophysiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/146608200300079536","article-title":"World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial Revisited: Revised Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis","volume":"1","author":"Brooks","year":"2000","journal-title":"Amyotroph. Lateral Scler. Other Mot. Neuron Disord."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a Biological Definition of Alzheimer\u2019s Disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:15:26Z","timestamp":1760127326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,20]]},"references-count":25,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411682"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411682","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,20]]}}}